57. Jahrgang - Supplement Nr. 13 - Oktober 2016

Limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy

Schlüsselwörter
Limb-girdle muscular dystrophy; ICD 10: G.71.0

Keywords
Limb-girdle muscular dystrophy; ICD 10: G.71.0

Zusammenfassung
Dieser Beitrag enthält keine Zusammenfassung

Summary

Limb-Girdle muscular dystrophy (LGMD) is a group of genetic muscle diseases characterized pathophysiologically by a mismatch between muscle breakdown and muscle repair, and it has a frequency of 1 in 15000. The main clinical features include proximal muscle weakness involving hip and shoulder girdles, elevated creatine kinase (although serum CK level is not an absolute secreening test for all LGMD) and a wide range of age of onset, from early childhood to late adulthood. Clinical classification is based on the distribution of weakness early in the course and on the age of presentation. It may be difficult to reach a precise diagnosis because of the wide clinical and genetic variability, and the different relative local frequencies of the different forms. The base of the diagnosis includes a clinical thorough evaluation, electrodiagnostic testing, muscle biopsy, imunohistochemistry and genetic analysis. These disorders may be either autosomal recessive (LGMD2) or dominant (LGMD1), and there are a number of different proteins involved, which allow a further classification of LGMD: LGMD 1A (myotilin), LGMD 1B (lamin A/C), LGMD 1C (caveolin 3), LGMD 2A (calpain-3), LGMD 2B (dysferlin), LGMD 2C-F (sarcoglycans), LGMD 2G (telethomin), LGMD 2H (TRIM 32), LGMD 2I (FKRP), LGMD 2J (titin), LGMD2L (anoctamin 5).

There are different disorders that must be taken in account in these patients, some of them sharing similar gene involvement; among these disorders we should include nuclear envelopathies (Emery-Dreifuss muscular dystrophy), Bethlem myopathy/Ulrich disease, and milder presentations of dystrophinopathies (Becker muscular dystrophy and women who are manifesting dystrophinopathy gene carriers). Diagnostic evaluation depends on inmunostaining or blotting, although these tests may be difficult to be properly interpreted. Genetic testing is somewhat limited on a practice basis to the research setting, but newer technologies (such as next generation sequencing panels) are actually significantly less expensive than muscle biopsy and provide a definitive diagnosis. The importance of genetic testing must not be overlooked because it may allow genetic counselling and prediction of other organ system involvement, like cardiomyopathy and respiratory failure.

The main issue when performing an anaesthetic procedure in these patients, deals with the risk of cardiac involvement (presence of cardiac myopathy and cardiac arrhythmia in LGMD 1A, 1B, 2C-F, 2I) and respiratory failure (LGMD 1A, 1B, 2C-F, 2I, 2J). In the case of LGMD 1B, pacemaker and implantable cardioverter defibrillator may be needed because of conduction disorders, and regarding LGMD 2I, 50% of the patients in this group may suffer from dilated cardiomyopathy.

We must keep in mind whenever facing a surgical procedure that this patients may have an increased sensitivity to the effect of anaesthetics and neuromuscular blocking agents. Although there is scarce evidence supporting an increased risk of malignant hyperthermia, there is a higher risk of suffering disease related cardiac complications and acute rhabdomyolysis when exposed to inhaled anaesthetics, and succinylcholine should be avoided as in many muscle disease because of being associated to life-threatening hyperkalemia.